crossing96/oncoscreening huggingface dataset:
PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy.	BACKGROUND AND OBJECTIVE: Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility. METHODS: Patients with localized MIBC received two doses of nivolumab (480 mg) alone (cohort 1) or with lirilumab (240 mg; cohort 2) prior to RC. Cohorts were enrolled sequentially. The key eligibility criteria were cT2-4aN0-1M0 stage and cisplatin ineligibility/refusal. The primary endpoint was the rate of grade (G) ≥3 treatment-related adverse events (TRAEs) as per Common Terminology Criteria for Adverse Events version 5.0. The key secondary endpoints included the proportion of patients who underwent RC >6 wk after the last dose, CD8+ T-cell density change between pretreatment transurethral resection of bladder tumor (TURBT) and post-treatment RC, ypT0N0, <ypT2N0 rates, 2-yr recurrence-free survival (RFS), and OS. KEY FINDINGS AND LIMITATIONS: Among 43 patients enrolled (n = 13, cohort 1; n = 30, cohort 2), 13 and 29 completed intended neoadjuvant therapy, respectively, in cohorts 1 and 2, and 41 underwent RC. The median time from the last dose to RC was 4 wk. The G3 TRAEs occurred in 0% (90% confidence interval [CI] 0-21%) of patients in cohort 1 and 7% (90% CI 1-20%) in cohort 2; all these TRAEs resolved and no G4/5 TRAEs occurred. No patient had delayed RC for >6 wk. In cohorts 1 and 2, ypT0N0 rates for patients with MIBC and RC were 17% and 21%, <ypT2N0 rates were 25% and 32%, 2-yr RFS rates were 73% and 71%, and 2-yr OS rates were 82% and 89%, respectively. CD8+ T-cell density increased significantly from TURBT to RC in cohort 2. CONCLUSIONS AND CLINICAL IMPLICATIONS: Neoadjuvant nivolumab-based immunotherapy was safe, feasible, and well tolerated in cisplatin-ineligible patients with MIBC. Although ypT0N0 rates were lower than expected, 2-yr survival rates seem to be comparable with those of other neoadjuvant immunotherapy trials. Nivolumab is being evaluated in the CA-017-078 trial (NCT03661320). PATIENT SUMMARY: For patients with muscle-invasive bladder cancer unable to receive cisplatin-based chemotherapy, treatment with nivolumab without and with lirilumab prior to radical cystectomy was safe, feasible, and well tolerated. Nivolumab-based immunotherapy showed lower pathologic response rates than but similar survival rates to other neoadjuvant immunotherapy trials.	bladder
Extraperitonealization of the ileal conduit decreases the risk of parastomal hernia: A single-center, randomized clinical trial.	Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.	bladder
Expression of EPB41L2 in Cancer-Associated Fibroblasts: Prognostic Implications for Bladder Cancer and Response to Immunotherapy.	BACKGROUND: Immunotherapy response in patients with bladder cancer (BLCA) treated with immune checkpoint inhibitors (ICIs) is variable. The accurate evaluation of immunotherapy efficacy may be facilitated by the tumor microenvironment (TME). Erythrocyte membrane protein band 4.1 like 2 (EPB41L2), a cytoskeletal protein with a regulatory role in the TME was intensively investigated to determine its biological characterization, clinical relevance, and predictive value for immunotherapy in BLCA. METHODS: Comprehensive bioinformatics and statistical analyses were conducted to examine gene expression profile, TME components, immune contexture, molecular features, and prediction of immunotherapy response. Immunohistochemistry (IHC) validated the results of the bioinformatics analysis. Association between immune checkpoint genes (ICGs) and EPB41L2-based risk stratification was validated in the IMvigor210 cohort, and their association with ICI response was assessed. RESULTS: EPB41L2 mRNA levels were decreased in BLCA compared to normal tissue. IHC showed reduced EPB41L2 staining intensity in early BLCA tissue. Nevertheless, elevated EPB41L2 expression was observed in cancer-associated fibroblasts (CAFs) with higher histological grade and pathological stage. High EPB41L2 expression served as a poor prognostic factor for BLCA. Single-cell RNA-seq and further analyses revealed that EPB41L2 was mainly expressed in CAFs and promoted TME remodeling. EPB41L2(low)/ICGs(high) patients showed greater benefit from immunotherapy. Gene mutation analysis revealed a close relationship between EPB41L2 and the frequency of oncogenic mutations, including TP53 and FGFR3. CONCLUSION: Comprehensive analysis and IHC confirmed the upregulation of EPB41L2 in BLCA CAFs and its association with TME remodeling. EPB41L2 and ICG expression were identified as combinatorial biomarkers to predict the response to immunotherapy.	bladder
HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer.	INTRODUCTION: Predicting the response to Bacillus Calmette-Guérin (BCG) therapy in high-risk patients with non-muscle invasive bladder cancer (NMIBC) is crucial, as failure may necessitate interventions, such as radical cystectomy or salvage therapy. With the recent classification of genetic class 2a (which has HER2 protein abundance as its signature mutation of ERBB2), evaluating its prognostic role and relationship with BCG response could yield important results. METHODS: This retrospective study included 160 patients with NMIBC who underwent transurethral resection of bladder tumors at Gangneung Asan Hospital between 2000 and 2013 and were stratified based on the European Organization for Research and Treatment of Cancer (EORTC) risk criteria. In addition, we analyzed a subset of 67 patients who had received BCG induction therapy to identify factors predictive of BCG treatment response. Univariate and multivariate analyses were used to assess the impact of clinicopathological factors, HER2 positivity, and EORTC risk on recurrence, progression, survival, and BCG response. Each variable's prognostic significance was determined using the Kaplan-Meier analysis. The tumor microenvironments (TMEs) were evaluated in relation to HER2 and EORTC risk. RESULTS: Patients with HER2+ had a higher median age, a greater prevalence of high-grade tumors, and more frequent recurrences. The univariate analysis demonstrated that the HER2+, intermediate (vs. low-risk) high (vs. low-risk), and EORTC recurrence risk groups were significantly associated with recurrence. In patients treated with BCG, only the HER2+ status predicted recurrence. In the univariate analysis for progression, age, high EORTC progression risk (vs. low-to-intermediate), HER2+, and programmed death-ligand 1 positive (PD-L1+) were significant factors. In multivariate analyses for progression, age, high EORTC progression risk, and PD-L1+ were significant factors for progression. HER2 expression was associated with the TME, influencing the proportion of PD-L1+ cells, as well as other markers of PD-1, CD8, and Ki67. CONCLUSION: The HER2+ status may be related to genetic characteristics that appear more frequently in older age, which suggests a potential for predicting the recurrence and response to BCG treatment. Additionally, analyzing TME trends of aggressive adaptive immune response characterized by HER2 expression provides insight into recurrence and BCG response mechanisms.	bladder
A new era for bladder cancer: Enfortumab vedotin and pembrolizumab milestone approval.	Cisplatin-based combos have become first-line treatment regimens in standard of care because of their high overall survival improvement. Despite being the first-line therapy, due to its side effects, roughly half of all patients suffering from Metastatic urothelial cancer are ineligible for it. To address this issue, scientists have been developing highly specific antibody-drug conjugates to address this issue. For locally advanced or metastatic bladder cancer, a combination of Padcev (enfortumab vedotin-ejfv) with pembrolizumab (Keytruda) has been authorized by the FDA as a first-line treatment and has shown promising outcomes in patients with metastatic urothelial carcinoma who are ineligible for cisplatin-based combinations.	bladder
Therapeutic Potential of Regorafenib in Cisplatin-Resistant Bladder Cancer with High Epithelial-Mesenchymal Transition and Stemness Properties.	Bladder cancer is becoming one of the most common malignancies across the world. Although treatment strategy has been continuously improved, which has led to cisplatin-based chemotherapy becoming the standard medication, cancer recurrence and metastasis still occur in a high proportion of patients because of drug resistance. The high efficacy of regorafenib, a broad-spectrum kinase inhibitor, has been evidenced in treating a variety of advanced cancers. Hence, this study investigated whether regorafenib could also effectively antagonize the survival of cisplatin-resistant bladder cancer and elucidate the underlying mechanism. Two types of cisplatin-resistant bladder cancer cells, T24R1 and T24R2, were isolated from T24 cisplatin-sensitive bladder cancer cells. These cells were characterized, and T24R1- and T24R2-xenografted tumor mice were created to examine the therapeutic efficacy of regorafenib. T24R1 and T24R2 cells exhibited higher expression levels of epithelial-mesenchymal transition (EMT) and stemness markers compared to the T24 cells, and regorafenib could simultaneously inhibit the viability and the expression of EMT/stemness markers of both T24R1 and T24R2 cells. Moreover, regorafenib could efficiently arrest the cell cycle, promote apoptosis, and block the transmigration/migration capabilities of both types of cells. Finally, regorafenib could significantly antagonize the growth of T24R1- and T24R2-xenografted tumors in mice. These results demonstrated the therapeutic efficacy of regorafenib in cisplatin-resistant bladder cancers. This study, thus, provides more insights into the mechanism of action of regorafenib and demonstrates its great potential in the future treatment of cisplatin-resistant advanced bladder cancer patients.	bladder
Metabolomic Signatures of Treatment Response in Bladder Cancer.	Bladder cancer (BC) stands as one of the most prevalent urological malignancies, with over 500 thousand newly diagnosed cases annually. Treatment decisions in BC depend on factors like the risk of recurrence, the type of tumor, and the stage of the disease. While standard therapeutic approaches encompass transurethral resection of the bladder tumor, radical cystectomy, and chemo- or immunotherapy, these methods exhibit limited efficacy in mitigating the aggressive and recurrent nature of bladder tumors. To overcome this challenge, it is crucial to develop innovative methods for monitoring and predicting treatment responses among patients with BC. Metabolomics is gaining recognition as a promising approach for discovering biomarkers. It has the potential to reveal metabolic disruptions that precisely reflect how BC patients respond to particular treatments, providing a revolutionary method to improve accuracy in monitoring and predicting outcomes. In this article, we present a comprehensive review of studies employing metabolomics approaches to investigate the metabolic responses associated with different treatment modalities for BC. The review encompasses an exploration of various models, samples, and analytical techniques applied in this context. Special emphasis is placed on the reported changes in metabolite levels derived from these studies, highlighting their potential as biomarkers for personalized medicine in BC.	bladder
Is Systemic Immune-Inflammation Index a Real Non-Invasive Biomarker to Predict Oncological Outcomes in Patients Eligible for Radical Cystectomy?	Background and Objectives: To assess the potential prognostic role of the systemic immune-inflammation index (SII) in predicting oncological outcomes in a cohort of patients treated with radical cystectomy (RC). Materials and Methods: From 2016 to 2022, a retrospective monocentric study enrolled 193 patients who were divided into two groups based on their SII levels using the optimal cutoff determined by the Youden index. The SII was obtained from a preoperative blood test approximately one month before RC. Univariable and multivariable logistic regression analyses were conducted to investigate the capacity of SII to predict lymph node invasion (N), advanced pT stage (pT3/pT4), and locally advanced condition at the time of RC. Multivariable Cox regression models adjusted for preoperative and postoperative features were used to analyze the prognostic effect of SII on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The optimal cutoff value of the SII was 640.27. An elevated SII was seen in 113 (58.5%) patients. Using the multivariable preoperative logistic regression models, an elevated SII was correlated with nodal invasion (N; p = 0.03), advanced pT stage (p = 0.04), and locally advanced disease (p = 0.005), with enhancement of AUCs for predicting locally advanced disease (p = 0.04). In multivariable Cox regression models that considered preoperative clinicopathologic factors, an elevated SII was linked to poorer RFS (p = 0.005) and OS (p = 0.01). Moreover, on multivariable Cox regression postoperative models, a high SII was linked to RFS (p = 0.004) and to OS (p = 0.01). Conclusions: In this monocentric retrospective study, higher preoperative SII values predicted worse oncological outcomes in patients with bladder cancer (BCa) who underwent RC.	bladder
Oncologic outcomes of intravesical therapy in the management of nonmuscle invasive bladder cancer with variant histology.	PURPOSE: There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center. MATERIALS AND METHODS: A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific, and overall survival. Survival time was computed from the date of initiation of intravesical therapy to the date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan-Meier method with log rank was utilized to compare survival time between VH sub-groups. RESULTS: Ninety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval [CI]: 2-46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes. CONCLUSION: In this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment.	bladder
The Role of c-MET as a Biomarker in Patients with Bladder Cancer Treated with Radical Chemo-Radiotherapy.	BACKGROUND: Bladder cancer is a highly aggressive cancer, and muscle invasive urothelial carcinoma (MIUC) requires aggressive strategy. Concomitant chemo-radiotherapy (CRT) appears as a therapeutic option that allows bladder sparing. No biomarker is currently available to optimally select patients for CRT. METHODS: We retrospectively enrolled patients with MIUC who were treated in a curative setting with CRT. Based on c-MET expression in pre-treatment tumor tissue, patients were stratified into two groups: no expression of c-MET (group A) and expression of c-MET (group B). We evaluated the outcome of these patients based on c-MET expression. RESULTS: After a median follow-up of 40 months, 13 patients were enrolled in this analysis, 8 in group A and 5 in group B. The disease recurrence was 25% in group A and 100% in group B. Compared to group A, patients from group B experienced more frequent and more rapid recurrence in terms of metastases; the 3-year metastatic recurrence rate was 13% and 100%, respectively. The c-MET expression was also associated with a higher rate of cancer-related deaths. CONCLUSIONS: In this retrospective analysis, c-MET expression was associated with worse disease-free survival and survival in patients treated radically with CRT.	bladder
Identifying Optimal Candidates for Trimodality Therapy among Nonmetastatic Muscle-Invasive Bladder Cancer Patients.	(1) Background: This research aims to identify candidates for trimodality therapy (TMT) or radical cystectomy (RC) by using a predictive model. (2) Methods: Patients with nonmetastatic muscle-invasive bladder cancer (MIBC) in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. The clinical data of 2174 eligible patients were extracted and separated into RC and TMT groups. To control for confounding bias, propensity score matching (PSM) was carried out. A nomogram was established via multivariable logistic regression. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to assess the nomogram's prediction capacity. Decision curve analysis (DCA) was carried out to determine the nomogram's clinical applicability. (3) Results: After being processed with PSM, the OS of the RC group was significantly longer compared with the TMT group (p < 0.001). This remarkable capacity for discrimination was exhibited in the training (AUC: 0.717) and validation (AUC: 0.774) sets. The calibration curves suggested acceptable uniformity. Excellent clinical utility was shown in the DCA curve. The RC and RC-Beneficial group survived significantly longer than the RC and TMT-Beneficial group (p < 0.001) or the TMT group (p < 0.001). However, no significant difference was found between the RC and TMT-Beneficial group and the TMT group (p = 0.321). (4) Conclusions: A predictive model with excellent discrimination and clinical application value was established to identify the optimal patients for TMT among nonmetastatic MIBC patients.	bladder
Effect of subsequent bladder cancer on survival in upper tract urothelial carcinoma patients post-radical nephroureterectomy: a systematic review and meta-analysis.	BACKGROUND: Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. METHODS: PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). RESULTS: Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001). CONCLUSIONS: SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.	bladder
Predictors of response to neoadjuvant therapy in urothelial cancer.	Neoadjuvant cisplatin-based chemotherapy (NACC) followed by radical cystectomy is the standard treatment for localized muscle-invasive bladder cancer (MIBC). Patients who achieve a complete pathological response following NACC have better overall survival than those with residual disease. However, a subset of patients does not derive benefit from NACC while experiencing chemotherapy-related side effects that may delay cystectomy, which can be detrimental. There is a need for predictive and prognostic biomarkers to better stratify patients who will derive benefits from NACC. This review summarizes the currently available literature on various predictors of response to neoadjuvant chemotherapy. Covered predictors include clinical factors, treatment regimens (including chemotherapy and immunotherapy), histological predictors, and molecular predictors such as DNA repair genes, p53, FGFR3, ERBB2, Bcl-2, EMMPRIN, survivin, choline-phosphate cytidylyltransferase-α, epigenetic markers, immunological markers, other molecular predictors and gene expression profiling. Further, we elaborate on the potential role of neoadjuvant immunotherapy and the correlative biomarkers of response.	bladder